Neurology Commons^™

The Tfeb-Tgif1 Axis Regulates Emt In Mouse Epicardial Cells, Elena Astanina, Gabriella Doronzo, Davide Corà, Francesco Neri, Salvatore Oliviero, Tullio Genova, Federico Mussano, Emanuele Middonti, Edoardo Vallariello, Chiara Cencioni, Donatella Valdembri, Guido Serini, Federica Limana, Eleonora Foglio, Andrea Ballabio, Federico Bussolino

Duncan NRI Faculty and Staff Publications

Epithelial-mesenchymal transition (EMT) is a complex and pivotal process involved in organogenesis and is related to several pathological processes, including cancer and fibrosis. During heart development, EMT mediates the conversion of epicardial cells into vascular smooth muscle cells and cardiac interstitial fibroblasts. Here, we show that the oncogenic transcription factor EB (TFEB) is a key regulator of EMT in epicardial cells and that its genetic overexpression in mouse epicardium is lethal due to heart defects linked to impaired EMT. TFEB specifically orchestrates the EMT-promoting function of transforming growth factor (TGF) β, and this effect results from activated transcription of thymine-guanine-interacting …

Catatonia In The General Hospital: A Case Series Wading Through Diagnostic & Management Challenges, Shireen Najam, Marium Mansoor, Muhammad Yusuf Hafiz, Alviya Shafique, Ifrah Hambal, Banafsha Gul, Tania Nadeem

Pakistan Journal of Neurological Sciences (PJNS)

Catatonia is a cluster of affective, behavioral, and motor symptoms. Its causes are multifactorial ranging from severe and untreated psychiatric illnesses to neurological diseases and other general medical conditions. It is estimated that 20% of catatonia causes are due to medical conditions out of which two thirds are due to an underlying neurological condition which might include encephalitis, neural injury, developmental disorders, structural brain pathology, or seizures. Symptoms of catatonia can wax and wane, fluctuating between the retarded and the excited type within hours making it more difficult to identify and diagnose. If left untreated, catatonia can lead to multiple …

Mr Textural Features (Radiomics) For Predicting Response To Treatment In Patients With Intracranial Tuberculoma: A Retrospective Cross-Sectional Study, Muhammad Awais, Shahmeer Khan, Mohammad Wasay, Muhammad Azeemuddin, Ayesha Shoukat, Hafsa Khan

Pakistan Journal of Neurological Sciences (PJNS)

Background and objective: MR based radiomics can potentially response to treatment in intracranial tuberculoma, but very scarce literature is available in this regard. The purpose of this study was to determine whether MR based radiomic features can be used to predict response to antituberculosis (AT) treatment. Methods: Data of patients with intracranial tuberculomas who underwent MR imaging and AT treatment at our institution during the last 10 years was analyzed. In each case follow-up imaging performed at 6 months post initiation of treatment was reviewed to establish response to treatment. The textural analysis was performed by two consultant neuroradiologists, using …

Long-Term Effectiveness Of Ivig Maintenance Therapy In 36 Patients With Gad Antibody-Positive Stiff-Person Syndrome., Jessica Yi, Marinos Dalakas

Department of Neurology Faculty Papers

BACKGROUND AND OBJECTIVES: IVIg has been the preferred immunotherapy in stiff-person syndrome (SPS) based on a 3-month controlled trial, but whether it is also effective in inducing long-term benefits or arresting disease progression is unknown. The information is needed because SPS is a progressively disabling disease and IVIg is liberally used as chronic therapy without efficacy data. The present study explores the long-term effects of IVIg in the largest cohort of well-characterized patients with SPS followed by the same clinicians over 10 years.

METHODS: Data of 36 patients (32 glutamic acid decarboxylase [GAD] positive), diagnosed and treated with monthly maintenance …

Pediatric Stroke: A Review, Tipu Sultan

Pakistan Journal of Neurological Sciences (PJNS)

Background and objectives: Pediatric Stroke is a neurological disorder in which the patient suffers with two or more Pediatric stroke is a focal neurological deficit lasting more than 24 hours because of stenosis, occlusion or rupture of cerebral blood vessels. Variable etiological factors are involved ranging from cardiac, haematological, infectious, immune mediated to arteriopathies which is emerging as most important cause of arterial ischemic stroke in children. In this review article we will discuss paediatric stroke with its epidemiology, etiological factors in particular arteriopathies, diagnostic modalities, management protocols and outcome.

Methods: We searched stroke in Pubmed and found 15315 articles, …

Tele-Stroke Care In Pakistan, Nurose Karim Md

Pakistan Journal of Neurological Sciences (PJNS)

No abstract provided.

Temporal Lobe Epilepsy With Hippocampus Sclerosis: Prevalence, Etiology, And Treatment Options With Herbal Medicines, Muhammad Wasim, Mehr Musani, Hasan Salman Siddiqi, Saara Muddasir, Bushra Amin, Fazal Manzoor Arain

Pakistan Journal of Neurological Sciences (PJNS)

Background and objectives: Epilepsy is a neurological disorder in which the patient suffers with two or more unprovoked seizures. It is one of the most common neurological disorders worldwide, affecting more than 70 million people. Currently various modes of effective treatments are available, but still there are many cases that remain drug resistant. Hence, there is a need to explore herbal medications for the treatment of drug resistant epilepsy.

Methods: Recent reviews and research articles (2000-2022) from PubMed and Google Scholar have been explored.

Review: Based on etiology, there are six categories of epilepsy: Genetic, Structural, Metabolic, Immune, Infectious, and …

Predictors Of Early Seizures After First Acute Stroke, Malik Muhammad Adil, Sumaira Nabi, Maryam Khalil, Zeeshan Munawar, Nayab Aslam, Zaid Waqar

Pakistan Journal of Neurological Sciences (PJNS)

Background and objective: There is a lack of local data regarding the frequency and predictors of early seizures after stroke. The objective of this study was to determine the frequency of early seizures after stroke and identify the predictors which lead to them after first acute stroke.

Methods: This cross-sectional observational study was conducted in the Department of Neurology, Pakistan Institute of Medical Sciences, Islamabad from October 2021 to June 2022. A total of 310 consecutive eligible patients of acute stroke were recruited. Key inclusion criteria included any patient of >20 years of age with confirmed diagnosis of stroke on …

Hypodensities Within Hematoma Predict Outcome After Spontaneous Intracerebral Hemorrhage, Maryam Khalil, Sumaira Nabi, Amjad Mahmood Khan, Zeeshan Munawar, Samar Naik, Zaid Waqar, Malik Muhammad Adil, Mazhar Badshah

Pakistan Journal of Neurological Sciences (PJNS)

Background and objective: Radial nerve is injured due to a variety of reasons. The objective of this study was to determine the clinical spectrum, risk factors and electrophysiologic aspect of radial nerve injury presenting to a tertiary care hospital in Lahore.

Methods: This descriptive prospective cross-sectional study was conducted at department of Neurology, Mayo hospital Lahore from July 2022 to December 2022 and comprised patients with isolated radial nerve injury on the basis of history and clinical examination regardless of their gender, above 15 years of age. NCS/EMG was done on a Japanese machine Nihon Kohden by an expert as …

Experience With Anti Nmda Receptor Antibody Encephalitis In A Tertiary Care Hospital In Pakistan, Haris Majid Rajput, Zaid Waqar, Muhammad Hassan, Neelma Naz Khattak, Umair Hassan, Iqra Athar, Mazhar Badshah Badshah

Pakistan Journal of Neurological Sciences (PJNS)

Background and objective: Anti NMDA receptor (Anti-NMDAR) antibody encephalitis is an increasingly recognized form of auto immune encephalitis. The objective of this study was to determine the demographic, clinical and laboratory factors associated with this syndrome.

Methods: All cases presenting to neurology, Pakistan institute of medical sciences, Islamabad, from June 2017 till January 2020 were reviewed retrospectively. Patients fulfilling the diagnostic criteria for Anti NMDA receptor (Anti-NMDAR) antibody encephalitis were included. All patients were evaluated with cerebrospinal fluid (CSF)routine examination, MRI brain, autoimmune encephalitis profile and for presence of oligoclonal bands (OCB) in CSF. Statistical analysis was done using SPSS …

Anti-Nmda Receptor Encephalitis Presenting With Severe Episodic Hypertension: A Case Report, Tehreem Arshad, Musarrat Hussain, Abdul Wahab Yousafzai, Arsalan Ahmad

Pakistan Journal of Neurological Sciences (PJNS)

Anti-N-methyl-D-aspartate receptor (Anti-NMDAR) encephalitis is one of the most commonly emerging autoimmune encephalitis in children and young adults in recent years. Clinical manifestations range from prodromal symptoms to seizures, movement disorder, psychiatric manifestations, cognitive/speech impairment, and autonomic dysfunction. Our case presented with initial symptoms of severe episodic hypertension, sweating, agitation, and tachycardia. She received early care for pheochromocytoma and panic disorder in Qatar, but there was no relief. Three weeks later, she presented in our emergency room with seizures, cognitive/speech impairment, and orofacial dyskinesia. Electroencephalography (EEG) revealed right hemispheric delta activity and cerebrospinal fluid CSF anti-NMDA Receptor IgG was positive. …

Clinical Spectrum, Risk Factors And Electrophysiologic Aspect Of Radial Nerve Injury, Arfah Kanwal, Safia Bano, Ubaid Ullah, Ahsan Numan

Pakistan Journal of Neurological Sciences (PJNS)

ABSTRACT

Background and objective: Radial nerve is injured due to a variety of reasons. The objective of this study was to determine the clinical spectrum, risk factors and electrophysiologic aspect of radial nerve injury presenting to a tertiary care hospital in Lahore.

Methods: This descriptive prospective cross-sectional study was conducted at department of Neurology, Mayo hospital Lahore from July 2022 to December 2022 and comprised patients with isolated radial nerve injury on the basis of history and clinical examination regardless of their gender, above 15 years of age. NCS/EMG was done on a Japanese machine Nihon Kohden by an expert …

Multiple Sclerosis In Pakistan: Collaborative Working To Improve Care, Sarah Razaq, Fahim Anwar

Pakistan Journal of Neurological Sciences (PJNS)

No abstract provided.

Retraction Notice, Editorial Team Pjns

Pakistan Journal of Neurological Sciences (PJNS)

Retraction Notice

Khan MI, Khan JI, Ahmed SI, Ali S. The epidemiology of stroke in a developing country (Pakistan). Pak J Neurol Sci. 2018;13(3):30-44.

A reader brought to our attention that the article titled “The epidemiology of stroke in a developing country (Pakistan)”, published in Volume 13, Issue 3, of Pakistan Journal of Neurological Sciences (PJNS) was a redundant (duplicate) publication. We investigated this complaint and found out that prior to its submission to PJNS on February 11 2018, this article had already been published almost verbatim in Journal of Neurology & Stroke on January 23, 2018.

Pharmacokinetic Evaluation Of Intravenous Vitamin C: A Classic Pharmacokinetic Study., Ping Chen, Greg Reed, Joyce Jiang, Yaohui Wang, Jean Sunega, Ruochen Dong, Yan Ma, Anna E. Esparham, Ryan Ferrell, Mark Levine, Jeanne Drisko, Qi Chen

Manuscripts, Articles, Book Chapters and Other Papers

Purpose: Intravenous vitamin C (IVC) is used in a variety of disorders with limited supporting pharmacokinetic data. Herein we report a pharmacokinetic study in healthy volunteers and cancer participants with IVC doses in the range of 1-100 g.

Methods: A pharmacokinetic study was conducted in 21 healthy volunteers and 12 oncology participants. Healthy participants received IVC infusions of 1-100 g; oncology participants received IVC infusions of 25-100 g. Serial blood and complete urine samples were collected pre-infusion and for 24 h post-infusion. Pharmacokinetic parameters were computed using noncompartmental methods. Adverse events were monitored during the study.

Results: In both cohorts, …

Idh1 Pr132h Ctdna And D-2-Hydroxyglutarate As Csf Biomarkers In Patients With Idh-Mutant Gliomas, Yoko Fujita, Luis Nunez-Rubiano, Antonio Dono, Allison Bellman, Mauli Shah, Juan C Rodriguez, Vasanta Putluri, Abu Hena Mostafa Kamal, Nagireddy Putluri, Roy F Riascos, Jay-Jiguang Zhu, Yoshua Esquenazi, Leomar Y Ballester

Faculty, Staff and Student Publications

INTRODUCTION: We aimed to evaluate IDH1 p.R132H mutation and 2-hydroxyglutarate (2HG) in cerebrospinal fluid (CSF) as biomarkers for patients with IDH-mutant gliomas.

METHODS: CSF was collected from patients with infiltrating glioma, and 2HG levels were measured by liquid chromatography-mass spectrometry. IDH1 p.R132H mutant allele frequency (MAF) in CSF-ctDNA was measured by digital droplet PCR (ddPCR). Tumor volume was measured from standard-of-care magnetic resonance images.

RESULTS: The study included 48 patients, 6 with IDH-mutant and 42 with IDH-wildtype gliomas, and 57 samples, 9 from the patients with IDH-mutant and 48 from the patients with IDH-wildtype gliomas. ctDNA was detected in 7 …

Development Of A Novel Pharmacophore Model To Screen Specific Inhibitors For The Serine-Threonine Protein Phosphatase Calcineurin, Abhisek Mukherjee, Karina Cuanalo-Contreras, Abha Sood, Claudio Soto

Faculty, Staff and Student Publications

Calcineurin (CaN) is a calcium/calmodulin-dependent serine/threonine phosphatase with a crucial role in cellular homeostasis. It is also the target of the Food and Drug Administration (FDA) approved immunosuppressant drugs FK506 and cyclosporine A. Recent work from our group and others indicated that an uncontrolled increase in CaN activity causes synaptic dysfunction and neuronal death in various models of neurodegenerative diseases associated with calcium dysregulation. Furthermore, pharmacological normalization of CaN activity can prevent disease progression in animal models. However, none of the FDA-approved CaN inhibitors bind CaN directly, leading to adverse side effects. The development of direct CaN inhibitors is required …

Treating Phantom Limb Pain: Cryoablation Of The Posterior Tibial Nerve, Matthew Fiala, Abana Azariah, Jean Woo, Ahmed Kamel Abdel Aal, Alexa Levey

Faculty, Staff and Student Publications

Phantom limb pain (PLP) is a complex pathophysiologic process involving both the central and peripheral nervous system for which there is no definitive treatment. The number of individuals living with amputated limbs is predicted to increase to 3.5 million by 2050, and up to 80% of these patients will have PLP. In this case report, we will demonstrate successful reduction of PLP in a patient with bilateral phantom toe pain utilizing nerve blockade and subsequent cryoablation of the posterior tibial nerves.

Duration Of Ischemia Affects Outcomes Independent Of Infarct Size In Stroke, Youngran Kim, Swapnil Khose, Osama O Zaidat, Ameer E Hassan, Johanna T Fifi, Ashish Nanda, Benjamin Atchie, Britton Woodward, Arnd Doerfler, Alejandro Tomasello, Albert J Yoo, Sunil A Sheth

Faculty, Staff and Student Publications

Background: Delays in endovascular reperfusion for patients with large vessel occlusion stroke are known to worsen outcomes, and the mechanism is believed to be time-dependent expansion of the ischemic infarction. In this study, we hypothesize that delays in onset to reperfusion (OTR) assert an effect on outcomes independent of effects of final infarct (FI).

Methods: We performed a subgroup analysis from the prospective multicenter COMPLETE (International Acute Ischemic Stroke Registry With the Penumbra System Aspiration Including the 3D Revascularization Device; Penumbra, Inc) registry for 257 patients with anterior circulation large vessel occlusion who underwent endovascular therapy with successful reperfusion (modified …

Altered Bladder-Related Brain Network In Multiple Sclerosis Women With Voiding Dysfunction, Zhaoyue Shi, Christof Karmonik, Amelia Soltes, Khue Tran, John A Lincoln, Timothy Boone, Rose Khavari

Faculty, Staff and Student Publications

Objectives:

A number of neuro-urology imaging studies have mainly focused on investigating the brain activations during micturition in healthy and neuropathic patients. It is, however, also necessary to study brain functional connectivity (FC) within bladder-related regions in order to understand the brain organization during the execution of bladder function. This study aims to identify the altered brain network associated with bladder function in multiple sclerosis (MS) women with voiding dysfunction through comparisons with healthy subjects via concurrent urodynamics (UDS)/fMRI.

Materials and Methods:

Ten healthy adult women and nine adult ambulatory women with clinically stable MS for ≥ 6 months and …

Mir-486 Is Essential For Muscle Function And Suppresses A Dystrophic Transcriptome, Adrienne Samani, Rylie M Hightower, Andrea L Reid, Katherine G English, Michael A Lopez, J Scott Doyle, Michael J Conklin, David A Schneider, Marcas M Bamman, Jeffrey J Widrick, David K Crossman, Min Xie, David Jee, Eric C Lai, Matthew S Alexander

Faculty, Staff and Student Publications

miR-486 is a muscle-enriched microRNA, or “myomiR,” that has reduced expression correlated with Duchenne muscular dystrophy (DMD). To determine the function of miR-486 in normal and dystrophin-deficient muscles and elucidate miR-486 target transcripts in skeletal muscle, we characterized mir-486 knockout mice (mir-486 KO). mir-486 KO mice developed disrupted myofiber architecture, decreased myofiber size, decreased locomotor activity, increased cardiac fibrosis, and metabolic defects were exacerbated in mir-486 KO:mdx5cv (DKO) mice. To identify direct in vivo miR-486 muscle target transcripts, we integrated RNA sequencing and chimeric miRNA eCLIP sequencing to identify key transcripts and pathways that contribute towards mir-486 …

The Impact Of Intraoperative Image-Guidance Modalities And Neurophysiologic Monitoring In The Safety Of Sacroiliac Fusions., Thiago Montenegro, Christian Hoelscher, Md, Kevin Hines, Md, Sara Thalheimer, Caio Matias, Bryan Wilent, James Harrop, Joshua E. Heller

Department of Neurosurgery Faculty Papers

STUDY DESIGN: Retrospective observational cohort.

OBJECTIVE: A review of efficiency and safety of fluoroscopy and stereotactic navigation system for minimally invasive (MIS) Sacroiliac (SI) fusion through a lateral technique.

METHODS: Retrospective analysis of an observational cohort of 96 patients greater than 18 years old, that underwent MIS SI fusion guided by fluoroscopy or navigation between January 2013 and April 2020 with a minimum of 3 months follow-up. Intraoperative neuromonitoring (IONM) with a variable combination of electromyography (EMG), somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs) was also utilized.

RESULTS: The overall complication rate in the study was 9.4%, and …

‘Fly-Ing’ From Rare To Common Neurodegenerative Disease Mechanisms, Mengqi Ma, Matthew J Moulton, Shenzhao Lu, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

Genome sequencing advances have enabled researchers and clinicians to probe vast numbers of human variants to distinguish pathogenic from benign variation. Model organisms have been critical in variant assessment and delineating molecular mechanisms of some of the diseases caused by these variants. The fruit fly, Drosophila melanogaster, has played a valuable role in this endeavor, taking advantage of its genetic technologies and established biological knowledge. In this review, we highlight the utility of the fly in studying the function of genes associated with rare neurological diseases that have led to a better understanding of common disease mechanisms. We emphasize …

Removal Of Kcnq2 From Parvalbumin-Expressing Interneurons Improves Anti-Seizure Efficacy Of Retigabine, Junzhan Jing, Corrinne Dunbar, Alina Sonesra, Ana Chavez, Suhyeorn Park, Ryan Yang, Heun Soh, Maxwell Lee, Anastasios V Tzingounis, Edward C Cooper, Xiaolong Jiang, Atul Maheshwari

Duncan NRI Faculty and Staff Publications

Anti-seizure drug (ASD) targets are widely expressed in both excitatory and inhibitory neurons. It remains unknown if the action of an ASD upon inhibitory neurons could counteract its beneficial effects on excitatory neurons (or vice versa), thereby reducing the efficacy of the ASD. Here, we examine whether the efficacy of the ASD retigabine (RTG) is altered after removal of the Kv7 potassium channel subunit KCNQ2, one of its drug targets, from parvalbumin-expressing interneurons (PV-INs). Parvalbumin-Cre (PV-Cre) mice were crossed with Kcnq2-floxed (Kcnq2fl/fl) mice to conditionally delete Kcnq2 from PV-INs. In these conditional knockout mice (cKO, PV-Kcnq2 …

Kctd7 Deficiency Induces Myoclonic Seizures Associated With Purkinje Cell Death And Microvascular Defects, Justine H Liang, Jonathan Alevy, Viktor Akhanov, Ryan Seo, Cory A Massey, Danye Jiang, Joy Zhou, Roy V Sillitoe, Jeffrey L Noebels, Melanie A Samuel

Duncan NRI Faculty and Staff Publications

Mutations in the potassium channel tetramerization domain-containing 7 (KCTD7) gene are associated with a severe neurodegenerative phenotype characterized by childhood onset of progressive and intractable myoclonic seizures accompanied by developmental regression. KCTD7-driven disease is part of a large family of progressive myoclonic epilepsy syndromes displaying a broad spectrum of clinical severity. Animal models of KCTD7-related disease are lacking, and little is known regarding how KCTD7 protein defects lead to epilepsy and cognitive dysfunction. We characterized Kctd7 expression patterns in the mouse brain during development and show that it is selectively enriched in specific regions as the brain matures. We further …

Evidence For An Association Between Coffin-Siris Syndrome And Congenital Diaphragmatic Hernia, Yoel Gofin, Xiaonan Zhao, Amanda Gerard, Fernando Scaglia, Michael F Wangler, Samantha A Schrier Vergano, Daryl A Scott

Duncan NRI Faculty and Staff Publications

Coffin-Siris syndrome (CSS) is an autosomal dominant neurodevelopmental syndrome that can present with a variety of structural birth defects. Pathogenic variants in 12 genes have been shown to cause CSS. Most of these genes encode proteins that are a part of the mammalian switch/sucrose non-fermentable (mSWI/SNF; BAF) complex. An association between genes that cause CSS and congenital diaphragmatic hernia (CDH) has been suggested based on case reports and the analysis of CSS and CDH cohorts. Here, we describe an unpublished individual with CSS and CDH, and we report additional clinical information on four published cases. Data from these individuals, and …

Limited Utility Of Structural Mri To Identify The Epileptogenic Zone In Young Children With Tuberous Sclerosis, Maaike Nijman, Edward Yang, Camilo Jaimes, Anna K Prohl, Mustafa Sahin, Darcy A Krueger, Joyce Y Wu, Hope Northrup, Scellig S D Stone, Joseph R Madsen, Aria Fallah, Jeffrey P Blount, Howard L Weiner, Leslie Grayson, E Martina Bebin, Brenda E Porter, Simon K Warfield, Sanjay P Prabhu, Jurriaan M Peters, Tacern Study Group

Faculty, Staff and Students Publications

BACKGROUND AND PURPOSE: The success of epilepsy surgery in children with tuberous sclerosis complex (TSC) hinges on identification of the epileptogenic zone (EZ). We studied structural MRI markers of epileptogenic lesions in young children with TSC.

METHODS: We included 26 children with TSC who underwent epilepsy surgery before the age of 3 years at five sites, with 12 months or more follow-up. Two neuroradiologists, blinded to surgical outcome data, reviewed 10 candidate lesions on preoperative MRI for characteristics of the tuber (large affected area, calcification, cyst-like properties) and of focal cortical dysplasia (FCD) features (cortical malformation, gray-white matter junction blurring, …

Future Opportunities For Research In Rescue Treatments, James W. Wheless, Daniel Friedman, Gregory L. Krauss, Vikram R. Rao, Michael R Sperling, Enrique Carrazana, Adrian L. Rabinowicz

Department of Neurology Faculty Papers

Clinical studies of rescue medications for seizure clusters are limited and are designed to satisfy regulatory requirements, which may not fully consider the needs of the diverse patient population that experiences seizure clusters or utilize rescue medication. The purpose of this narrative review is to examine the factors that contribute to, or may influence the quality of, seizure cluster research with a goal of improving clinical practice. We address five areas of unmet needs and provide advice for how they could enhance future trials of seizure cluster treatments. The topics addressed in this article are: (1) unaddressed end points to …

Phenotypic And Genetic Spectrum Of Atp6v1a Encephalopathy: A Disorder Of Lysosomal Homeostasis, Renzo Guerrini, Davide Mei, Katalin Kerti-Szigeti, Sara Pepe, Mary Kay Koenig, Gretchen Von Allmen, Megan T Cho, Kimberly Mcdonald, Janice Baker, Vikas Bhambhani, Zöe Powis, Lance Rodan, Rima Nabbout, Giulia Barcia, Jill A Rosenfeld, Carlos A Bacino, Cyril Mignot, Lillian H Power, Catharine J Harris, Dragan Marjanovic, Rikke S Møller, Trine B Hammer, Riikka Keski Filppula, Päivi Vieira, Clara Hildebrandt, Stephanie Sacharow, Luca Maragliano, Fabio Benfenati, Katherine Lachlan, Andreas Benneche, Florence Petit, Jean Madeleine De Sainte Agathe, Barbara Hallinan, Yue Si, Ingrid M Wentzensen, Fanggeng Zou, Vinodh Narayanan, Naomichi Matsumoto, Alessandra Boncristiano, Giancarlo La Marca, Mitsuhiro Kato, Kristin Anderson, Carmen Barba, Luisa Sturiale, Domenico Garozzo, Roberto Bei, Laura Masuelli, Valerio Conti, Gaia Novarino, Anna Fassio

Faculty, Staff and Student Publications

Vacuolar-type H+-ATPase (V-ATPase) is a multimeric complex present in a variety of cellular membranes that acts as an ATP-dependent proton pump and plays a key role in pH homeostasis and intracellular signalling pathways. In humans, 22 autosomal genes encode for a redundant set of subunits allowing the composition of diverse V-ATPase complexes with specific properties and expression. Sixteen subunits have been linked to human disease. Here we describe 26 patients harbouring 20 distinct pathogenic de novo missense ATP6V1A variants, mainly clustering within the ATP synthase α/β family-nucleotide-binding domain. At a mean age of 7 years (extremes: 6 weeks, youngest deceased …

Somatic Variants In Diverse Genes Leads To A Spectrum Of Focal Cortical Malformations, Dulcie Lai, Meethila Gade, Edward Yang, Hyun Yong Koh, Jinfeng Lu, Nicole M Walley, Anne F Buckley, Tristan T Sands, Cigdem I Akman, Mohamad A Mikati, Guy M Mckhann, James E Goldman, Peter Canoll, Allyson L Alexander, Kristen L Park, Gretchen K Von Allmen, Olga Rodziyevska, Meenakshi B Bhattacharjee, Hart G W Lidov, Hannes Vogel, Gerald A Grant, Brenda E Porter, Annapurna H Poduri, Peter B Crino, Erin L Heinzen

Faculty, Staff and Student Publications

Post-zygotically acquired genetic variants, or somatic variants, that arise during cortical development have emerged as important causes of focal epilepsies, particularly those due to malformations of cortical development. Pathogenic somatic variants have been identified in many genes within the PI3K-AKT-mTOR-signalling pathway in individuals with hemimegalencephaly and focal cortical dysplasia (type II), and more recently in SLC35A2 in individuals with focal cortical dysplasia (type I) or non-dysplastic epileptic cortex. Given the expanding role of somatic variants across different brain malformations, we sought to delineate the landscape of somatic variants in a large cohort of patients who underwent epilepsy surgery with hemimegalencephaly …